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Drug-Drug Interaction Study of Entinostat and Exemestane in Postmenopausal Women With ER+ Breast Cancer

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ClinicalTrials.gov Identifier: NCT02820961
Recruitment Status : Active, not recruiting
First Posted : July 1, 2016
Last Update Posted : June 21, 2018
Sponsor:
Information provided by (Responsible Party):
Syndax Pharmaceuticals

Brief Summary:
The purpose of this study is to determine the effect of exemestane on the pharmacokinetics (PK) of entinostat and to determine the effect of entinostat on the PK of exemestane in patients with locally recurrent or metastatic estrogen receptor positive (ER+) breast cancer. Additionally, this study will evaluate the safety and tolerability of entinostat in combination with exemestane, and assess the effectiveness of entinostat in combination with exemestane in terms of best overall response and overall survival.

Condition or disease Intervention/treatment Phase
Breast Cancer Estrogen Receptor Positive Breast Cancer Drug: entinostat Drug: exemestane Phase 1

Detailed Description:

SNDX-275-0130 is a Phase 1, two-cohort, open-label, drug-drug interaction study of entinostat and exemestane. All patients will be enrolled into one of two cohorts to receive either entinostat monotherapy followed by entinostat plus exemestane (Cohort 1), or exemestane monotherapy followed by exemestane plus entinostat (Cohort 2).

The cohorts will enroll sequentially, meaning that Cohort 1 will enroll prior to Cohort 2. Cohort 1 will evaluate exemestane's effect on the PK of entinostat. Cohort 2 will evaluate entinostat's effect on the PK of exemestane. In both Cohorts, each treatment cycle will be 28 days. Patients will participate in only one cohort.

All patients will be assessed at Screening and at specified times during the conduct of the study using standard clinical and laboratory assessment. Patients will also be assessed for tumor response per standard of care after the Screening Period. Response to treatment will be assessed by computerized tomography (CT), magnetic resonance imaging (MRI) and bone scans as appropriate. Patients will continue receiving their appropriate cycles of study treatment until tumor progression or adverse events (AEs) occur which necessitate discontinuing therapy as determined by the Investigator.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1, Two-Cohort, Open-Label, Drug-Drug Interaction Study of Entinostat and Exemestane in Postmenopausal Women With Locally Recurrent or Metastatic ER+ Breast Cancer
Actual Study Start Date : June 29, 2016
Estimated Primary Completion Date : December 2018
Estimated Study Completion Date : December 2018

Resource links provided by the National Library of Medicine

Drug Information available for: Exemestane

Arm Intervention/treatment
Active Comparator: Cohort 1
Cohort 1 will evaluate exemestane's effect on the PK of entinostat. Each treatment cycle is 28 days.
Drug: entinostat
An orally available histone deacetylases inhibitor (HDAC)
Other Names:
  • SNDX-275
  • MS-275

Drug: exemestane
Aromatase inhibitor
Other Names:
  • Aromasin
  • FCE-24304

Active Comparator: Cohort 2
Cohort 2 will enroll when Cohort 1 enrollment is complete. Cohort 2 will evaluate entinostat's effect on the PK of exemestane. Each treatment cycle is 28 days.
Drug: entinostat
An orally available histone deacetylases inhibitor (HDAC)
Other Names:
  • SNDX-275
  • MS-275

Drug: exemestane
Aromatase inhibitor
Other Names:
  • Aromasin
  • FCE-24304




Primary Outcome Measures :
  1. Cmax, maximum plasma concentration [ Time Frame: Approximately 1 year ]
  2. Tmax, time at which maximum plasma concentration was observed [ Time Frame: Approximately 1 year ]
  3. AUC0-t, area under the plasma concentration-time curve from time zero to the last measurable concentration [ Time Frame: Approximately 1 year ]
  4. AUC0-inf, area under the plasma concentration-time curve from time zero extrapolated to infinity [ Time Frame: Approximately 1 year ]
  5. T1/2, elimination half-life [ Time Frame: Approximately 1 year ]
  6. lambda z , apparent terminal phase elimination constant (λz) [ Time Frame: Approximately 1 year ]
  7. AUC0-τ where τ=168 hours for entinostat and τ=24 hours for exemestane [ Time Frame: Approximately 1 year ]
  8. Incidence of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), AEs resulting in the permanent discontinuation of study drug, and deaths occurring within 30-days of the last dose of study drug [ Time Frame: Approximately 1 year ]
  9. Changes from baseline in laboratory, vital signs, and electrocardiogram (ECG) values [ Time Frame: Approximately 1 year ]

Secondary Outcome Measures :
  1. Best overall tumor response [ Time Frame: Approximately 2 years ]
  2. Overall survival [ Time Frame: Approximately 2 years ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Postmenopausal female patients
  • Histologically or cytologically confirmed ER+ breast cancer at initial diagnosis and have locally recurrent or metastatic disease that has progressed to where the patient is a candidate to receive exemestane as determined by the Investigator
  • Patients receiving palliative radiation at the non-target lesions must be clinically stable prior to receiving the first dose of study treatment
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • Patient must have acceptable, applicable laboratory requirements
  • Patients may have a history of brain metastasis provided certain protocol criteria are met
  • Able to understand and give written informed consent and comply with study procedures

Exclusion Criteria:

  • Rapidly progressive or life-threatening metastases
  • Inability to swallow oral medications or gastrointestinal (GI) malabsorption syndromes
  • History of significant GI surgery as determined by Investigator
  • A medical condition that precludes adequate study treatment or increases patient risk
  • Currently enrolled in (or completed within 30 days prior to study drug administration) another investigational drug study

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02820961


Locations
United States, Colorado
Sarah Cannon Research Institute HealthONE
Denver, Colorado, United States, 80218
United States, Florida
Florida Cancer Specialists
Sarasota, Florida, United States, 34232
United States, Tennessee
Sarah Cannon Research Institute
Nashville, Tennessee, United States, 37203
Sponsors and Collaborators
Syndax Pharmaceuticals
Investigators
Study Director: Michael Meyers, MD, PhD Syndax Pharmaceuticals

Responsible Party: Syndax Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02820961     History of Changes
Other Study ID Numbers: SNDX-275-0130
First Posted: July 1, 2016    Key Record Dates
Last Update Posted: June 21, 2018
Last Verified: June 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Syndax Pharmaceuticals:
Breast Neoplasms
Breast Diseases
Exemestane
Protein Kinase Inhibitors
Aromatase Inhibitors
entinostat
Cancer of the Breast
Metastatic Breast Cancer
Hormone Receptor Positive Breast Cancer
Estrogen Receptor
ER+ Breast Cancer
Breast Tumor

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Exemestane
Entinostat
Aromatase Inhibitors
Antineoplastic Agents
Steroid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Estrogen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Histone Deacetylase Inhibitors